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Meta-Analysis
. 2013 Nov;62(5):853-9.
doi: 10.1161/HYPERTENSIONAHA.113.01148. Epub 2013 Sep 3.

Genome-wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci

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Free PMC article
Meta-Analysis

Genome-wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci

Tanika N Kelly et al. Hypertension. .
Free PMC article

Abstract

We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage 1) followed by replication study of up to 28,783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10(-3). No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10(-15)), rs2681492 at ATP2B1 (P=3.4×10(-7)), rs11191593 at NT5C2 (1.1×10(-6)), rs3824755 at CYP17A1 (P=1.2×10(-6)), and rs13149993 at FGF5 (P=2.4×10(-4)). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10(-5)) and rs11191593 at NT5C2 (P=1.1×10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10(-3)) and rs2681492 at ATP2B1 (P=9.0×10(-3)). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.

Keywords: blood pressure; genetics; genome-wide association study; hypertension; meta-analysis; polymorphism, single nucleotide.

Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Genome-wide association study (GWAS) meta-analysis results for MAP (a) and PP (b). Loci highlighted in red indicate the 2 Mb regions of SNPs which achieved genome-wide significance in stage-1 and joint analyses of stage-1 and stage-2 studies. Loci highlighted in black indicate the 2 Mb regions of SNPs which achieved borderline significance (P<1E-6) in the stage-1 GWAS meta-analysis. Loci highlighted in blue indicate the 2 Mb regions of SNPs which achieved genome-wide significance in the GWAS meta-analysis of Europeans (unless achieving P<1E-6 in the current study). Loci which achieved genome-wide significance in Europeans or East Asians are labeled (blue if originally identified in Europeans; black if originally identified in the current study).
Figure 2
Figure 2
Effect sizes and coded allele frequencies (CAF) for SNPs that showed evidence of trans-ethnic replication for MAP (a) and PP (b) in East Asian participants of the current GWAS meta-analysis. Effect sizes in the current study of East Asians are shown in black while those of the previous GWAS meta-analysis of Europeans are shown in red.

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